Coronary heart disease is generally thought to be caused by the narrowing of coronary arteries by atherosclerosis, i.e., the buildup of fatty deposits in the lining of the arteries. The process that may lead to atherosclerosis begins with the accumulation of excess fats and cholesterol in the blood. These substances infiltrate the lining of arteries, gradually increasing in size to form deposits commonly referred to as plaque or atherosclerotic occlusions. Plaques narrow the arterial lumen and impede blood flow. Blood cells may collect around the plaque, eventually creating a blood clot that may block the artery completely.
While the known procedures for treating plaque have gained wide acceptance and shown good efficacy for treatment of standard stenotic plaques, they may be ineffective, and possibly dangerous, when thrombotic conditions are superimposed on atherosclerotic plaques.
Tissue factor has been implicated in plaque/vascular thrombosis. For example, in human carotid plaque, tissue factor is co-localized with areas of plaque inflammation, predominantly to macrophages.
Tissue factor acts by activating Factor VII which activates Factor X that stimulates the conversion of prothrombin (II) into thrombin (IIa). Thrombin then acts to convert fibrinogen to fibrin monomer which then polymerizes to form a fibrin clot.
Because thrombosis causes most manifestations of atheroma, therapies that block thrombosis in a particular region of the vasculature are needed. The present invention provides such a therapy, as well as a novel method of administering the therapy.